The connexins are a group of GAP junction proteins, which form a hexamer
to compose a connexon. Clusters of connexons form a GAP junction through
which low molecular weight proteins may diffuse from cell to cell. Several
mammalian cells with malignant phenotypes exhibit decreased connexin
expression and GAP junction communication. There is a decrease in GAP
junctional communication in Src transformed cells. The decreased communication
appears to be associated with tyrosine phosphorylation of connexin
43. Activated c-Src phosphorylates the C-terminal tail of connexin 43 on
residue Tyr 265, resulting in a stable interaction between both proteins leading
to inhibition of GAP junctional communication. In addition to tyrosine
phosphorylation, connexin 43 has also been shown to be phosphorylated on
serine in the absence of Src kinases and on both serine and tyrosine in cells
expressing Src kinases such as pp60v-Src and/or c-Src.